Refractory cholinergic urticaria successfully treated with ketotifen

Four patients with cholinergic urticaria associated with additional cardiorespiratory manifestations are described. Two patients reported cold, in addition to heat and exercise, as a factor inducing symptoms. Prospective exercise challenge documented a rise in in plasma histamine sixfold to 20-fold above baseline values that accompanied onset of symptoms. All four subjects had proved refractory to conventional antihistamine therapy. Institution of ketotifen at doses ranging from 3 to 8 mg per day resulted in symptomatic improvement, and in all four subjects a repeat exercise challenge confirmed clinical improvement. In three subjects exercise challenge with ketotifen demonstrated blockade of mast cell-mediator release. Plasma histamine levels remained at baseline. In the fourth patient, histamine rose to about half the peak observed before ketotifen therapy. These findings confirm the observation that ketotifen is both an H1 histamine-receptor antagonist as well as a stabilizer of mast cell-mediator release. We speculate that ketotifen may prove more effective than conventional antihistamines in the management of severe urticaria.